The distribution of phosphatidylserine (PS) in the cell surface membrane is different between normal and neoplastic tissues. We will use this feature in designing a new family of STVTs (Selective Tumor Vascular Thrombogens) that for two reasons will increase their selectivity and efficacy: (i) PS is preferentially exposed on the outer leaf of the cell membrane of tumor and activated endothelial cells; (ii) the thrombogen incorporated into the STVT is only substantially active on microdomains on the surface of cells rich in anionic phospholipids. STVTs are designed to transiently and selectively interact with tumor vasculature causing the formation of thrombii that restrict the flow of nutrients and lead to infartive apoptosis and necrosis. STVTs will not initiate thrombosis of normal vessels. This proposal addresses a new class of STVTs that utilize cell surface exposed phosphatidylserine in the tumor microvasculature to selectively activate the thrombogenic cascade when it encounters the PS-rich surface. PROPOSED COMMERCIAL APPLICATION: Development of anti-cancer agents remains one of the most important activities of the biopharmaceutical industry. The need for more effective cancer therapy is readily apparent, as more than 1.5 million people in the U.S. get some type of cancer each year. This market is more than $10 billion per year.